tbuckley/cabot-search huggingface dataset:
Electroconductive Collagen‐Carbon Nanodots Nanocomposite Elicits Neurite Outgrowth, Supports Neurogenic Differentiation and Accelerates Electrophysiological Maturation of Neural Progenitor Spheroids
Authors: David J. Lomboni, Alp Ozgun, Tayline V. de Medeiros, William Staines, Rafik Naccache, John Woulfe, Fabio Variola
Journal: Advanced Healthcare Materials (2023)

Neuronal disorders are characterized by the loss of functional neurons and disrupted neuroanatomical connectivity, severely impacting the quality of life of patients. This study investigates a novel electroconductive nanocomposite consisting of glycine-derived carbon nanodots (GlyCNDs) incorporated into a collagen matrix and validates its beneficial physicochemical and electro-active cueing to relevant cells. To this end, this work employs mouse induced pluripotent stem cell (iPSC)-derived neural progenitor (NP) spheroids. The findings reveal that the nanocomposite markedly augmented neuronal differentiation in NP spheroids and stimulate neuritogenesis. In addition, this work demonstrates that the biomaterial-driven enhancements of the cellular response ultimately contribute to the development of highly integrated and functional neural networks. Lastly, acute dizocilpine (MK-801) treatment provides new evidence for a direct interaction between collagen-bound GlyCNDs and postsynaptic N-methyl-D-aspartate (NMDA) receptors, thereby suggesting a potential mechanism underlying the observed cellular events. In summary, the findings establish a foundation for the development of a new nanocomposite resulting from the integration of carbon nanomaterials within a clinically approved hydrogel, toward an effective biomaterial-based strategy for addressing neuronal disorders by restoring damaged/lost neurons and supporting the reestablishment of neuroanatomical connectivity.
Bedaquiline resistance in patients with drug-resistant tuberculosis in Cape Town, South Africa: a retrospective longitudinal cohort study
Authors: Brigitta Derendinger, Anzaan Dippenaar, Margaretha de Vos, Stella Huo, Rencia Alberts, Rebecca Tadokera, Jason Limberis, Frik Sirgel, Tania Dolby, Claudia Spies, Anja Reuter, Megan Folkerts, Christopher Allender, Darrin Lemmer, Annelies Van Rie, Sebastien Gagneux, Leen Rigouts, Julian te Riele, Keertan Dheda, David M Engelthaler, Robin Warren, John Metcalfe, Helen Cox, Grant Theron
Journal: The Lancet Microbe (2023)

Bedaquiline is a life-saving tuberculosis drug undergoing global scale-up. People at risk of weak tuberculosis drug regimens are a priority for novel drug access despite the potential source of Mycobacterium tuberculosis-resistant strains. We aimed to characterise bedaquiline resistance in individuals who had sustained culture positivity during bedaquiline-based treatment.
Radiotherapy to regional nodes in early breast cancer: an individual patient data meta-analysis of 14 324 women in 16 trials
Authors: Carolyn Taylor, David Dodwell, Paul McGale, Robert K Hills, Richard Berry, Rosie Bradley, Jeremy Braybrooke, Mike Clarke, Richard Gray, Francesca Holt, Zulian Liu, Hongchao Pan, Richard Peto, Ewan Straiton, Charlotte Coles, Fran Duane, Christophe Hennequin, Glenn Jones, Thorsten Kühn, Sileida Oliveros, Jens Overgaard, Kathy I Pritchard, Chang-Ok Suh, Graham Beake, Clare Boddington, Christina Davies, Lucy Davies, Vaughan Evans, Jo Gay, Lucy Gettins, Jon Godwin, Sam James, Amanda Kerr, Hui Liu, Elizabeth MacKinnon, Gurdeep Mannu, Theresa McHugh, Philip Morris, Mariko Nakahara, Simon Read, Hannah Taylor, John Ferguson, Hans Scheurlen, Stefano Zurrida, Viviana Galimberti, James Ingle, Pinuccia Valagussa, Umberto Veronesi, Stewart Anderson, Gong Tang, Bernard Fisher, Sophie Fossa, Kristin Valborg Reinertsen, Herman Host, Hyman Muss, Kaija Holli, Kathy Albain, Rodrigo Arriagada, John Bartlett, Elizabeth Bergsten-Nordström, Judith Bliss, Etienne Brain, Lisa Carey, Robert Coleman, Jack Cuzick, Nancy Davidson, Lucia Del Mastro, Angelo Di Leo, James Dignam, Mitch Dowsett, Bent Ejlertsen, Prue Francis, José Angel García-Sáenz, Rich Gelber, Michael Gnant, Matthew Goetz, Pam Goodwin, Pat Halpin-Murphy, Dan Hayes, Catherine Hill, Reshma Jagsi, Wolfgang Janni, Sibylle Loibl, Eleftherios Mamounas, Miguel Martín, Stuart McIntosh, Hirofumi Mukai, Valentina Nekljudova, Larry Norton, Yasuo Ohashi, Martine Piccart, Lori Pierce, Vinod Raina, Daniel Rea, Meredith Regan, John Robertson, Emiel Rutgers, Roberto Salgado, Dennis Slamon, Tanja Spanic, Joseph Sparano, Guenther Steger, Masakazu Toi, Andrew Tutt, Giuseppe Viale, Xiang Wang, Nicholas Wilcken, Norman Wolmark, Ke-Da Yu, David Cameron, Jonas Bergh, Sandra Swain, Tim Whelan, Philip Poortmans
Journal: The Lancet (2023)

Radiotherapy has become much better targeted since the 1980s, improving both safety and efficacy. In breast cancer, radiotherapy to regional lymph nodes aims to reduce risks of recurrence and death. Its effects have been studied in randomised trials, some before the 1980s and some after. We aimed to assess the effects of regional node radiotherapy in these two eras.
GPIbα–filamin A interaction regulates megakaryocyte localization and budding during platelet biogenesis
Authors: Marc L. Ellis, Antoine Terreaux, Imala Alwis, Rhyll Smythe, Jose Perdomo, Anita Eckly, Susan L. Cranmer, Freda H. Passam, Jessica Maclean, Simone M. Schoenwaelder, Zaverio M. Ruggeri, Francois Lanza, Samir Taoudi, Yuping Yuan, Shaun P. Jackson
Journal: Blood (2023)
Portable and Rapid Dual‐Biomarker Detection Using Solution‐Gated Graphene Field Transistors in the Accurate Diagnosis of Prostate Cancer
Authors: Minghua Deng, Huan Yang, Huibin Zhang, Chaoqian Li, Jingqiu Chen, Wei Tang, Xianbao Wang, Zhaowei Chen, Jinhua Li
Journal: Advanced Healthcare Materials (2023)

Prostate-specific antigen (PSA) is the common serum-relevant biomarker for early prostate cancer (PCa) detection in clinical diagnosis. However, it is difficult to accurately diagnose PCa in the early stage due to the low specificity of PSA. Herein, a new solution-gated graphene field transistor (SGGT) biosensor with dual-gate for dual-biomarker detection is designed. The sensing mechanism is that the designed aptamers immobilized on the surface of the gate electrodes can capture PSA and sarcosine (SAR) biomolecules and induce the capacitance changes of the electric double layers of SGGT. The limit of detections of PSA and SAR biomarkers can reach 0.01 fg mL
Controllable Adaptive Molybdate‐Oligosaccharide Nanoparticles Regulate M2 Macrophage Mitochondrial Function and Promote Angiogenesis via PI3K/HIF‐1α/VEGF Pathway to Accelerate Diabetic Wound Healing
Authors: Xiuhong Huang, Liqin Zheng, Yueshan Zhou, Shaonan Hu, Wancheng Ning, Simin Li, Ziling Lin, Shaohong Huang
Journal: Advanced Healthcare Materials (2023)

Abstract The complex wound environment of diabetic wounds leads to poor treatment efficacy, and the inflammatory disorders and vascular injury are the primary causes of death in such patients. Herein, a sprayable, controllable adaptive, pH‐responsive nanosystem of molybdate and oligosaccharide (CMO) is specially developed as an immunomodulatory and angiogenesis‐promotion material for diabetic wound healing. CMO exhibited pH‐responsive release of Mo 2+ and oligosaccharide (COS), specifically in response to the alkalescent environment observed in diabetic wounds. CMO provide an anti‐inflammatory environment by promoting M2 polarization through significantly stimulating macrophage mitochondrial function. Specifically, CMO with a certain concentration reduce reactive oxygen species (ROS) and tumor necrosis factor α (TNF‐α) expression, and upregulated mitochondrial membrane potential (MMP), superoxide dismutase (SOD), and interleukin 10 (IL‐10) expression in macrophages. Moreover, CMO facilitate angiogenesis via upregulating the PI3K/HIF‐1α/VEGF pathway—a critical process for the formation of new blood vessels that supply nutrients and oxygen to the healing tissue. Remarkably, CMO promote cell viability and migration of endothelial cells, and enhance the expression of angiogenic genes. In vitro and in vivo studies suggest this simple but powerful nanosystem targeting mitochondrial function has the potential to become an effective treatment for diabetic wound healing.
Targeting MTHFD2 to Exploit Cancer-Specific Metabolism and the DNA Damage Response
Authors: Louise Ramos, Martin Henriksson, Thomas Helleday, Alanna C. Green
Journal: Cancer Research (2023)

Abstract The one-carbon folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across numerous cancer types, promotes growth and metastasis of cancer, and correlates with poorer survival. Recent studies have developed small-molecule inhibitors to the isozymes MTHFD2 and MTHFD1 that show promise as anticancer agents through different mechanisms. This review discusses the current understanding of the function of MTHFD2 in cancer and the status of inhibitors for treating MTHFD2-overexpressing cancers.
Regulation of lymphoid-myeloid lineage bias through regnase-1/3-mediated control of Nfkbiz
Authors: Takuya Uehata, Shinnosuke Yamada, Daisuke Ori, Alexis Vandenbon, Amir Giladi, Adam Jelinski, Yasuhiro Murakawa, Hitomi Watanabe, Kazuhiro Takeuchi, Kazunori Toratani, Takashi Mino, Hisanori Kiryu, Daron M. Standley, Tohru Tsujimura, Tomokatsu Ikawa, Gen Kondoh, Markus Landthaler, Hiroshi Kawamoto, Hans-Reimer Rodewald, Ido Amit, Ryo Yamamoto, Masaki Miyazaki, Osamu Takeuchi
Journal: Blood (2023)

Regulation of lineage biases in hematopoietic stem and progenitor cells (HSPCs) is pivotal for balanced hematopoietic output. However, little is known about the mechanism behind lineage choice in HSPCs. Here, we show that messenger RNA (mRNA) decay factors regnase-1 (Reg1; Zc3h12a) and regnase-3 (Reg3; Zc3h12c) are essential for determining lymphoid fate and restricting myeloid differentiation in HSPCs. Loss of Reg1 and Reg3 resulted in severe impairment of lymphopoiesis and a mild increase in myelopoiesis in the bone marrow. Single-cell RNA sequencing analysis revealed that Reg1 and Reg3 regulate lineage directions in HSPCs via the control of a set of myeloid-related genes. Reg1- and Reg3-mediated control of mRNA encoding Nfkbiz, a transcriptional and epigenetic regulator, was essential for balancing lymphoid/myeloid lineage output in HSPCs in vivo. Furthermore, single-cell assay for transposase-accessible chromatin sequencing analysis revealed that Reg1 and Reg3 control the epigenetic landscape on myeloid-related gene loci in early stage HSPCs via Nfkbiz. Consistently, an antisense oligonucleotide designed to inhibit Reg1- and Reg3-mediated Nfkbiz mRNA degradation primed hematopoietic stem cells toward myeloid lineages by enhancing Nfkbiz expression. Collectively, the collaboration between posttranscriptional control and chromatin remodeling by the Reg1/Reg3-Nfkbiz axis governs HSPC lineage biases, ultimately dictating the fate of lymphoid vs myeloid differentiation.
Canonical BAF complex regulates the oncogenic program in human T-cell acute lymphoblastic leukemia
Authors: Kazunari Aoki, Mizuki Hyuga, Yusuke Tarumoto, Gohei Nishibuchi, Atsushi Ueda, Yotaro Ochi, Seiichi Sugino, Takashi Mikami, Hirokazu Kobushi, Itaru Kato, Koshi Akahane, Takeshi Inukai, Akifumi Takaori-Kondo, Junko Takita, Seishi Ogawa, Kosuke Yusa
Journal: Blood (2023)
A genetically encoded protein tag for control and quantitative imaging of CAR T cell therapy
Authors: Iris K. Lee, Nitika Sharma, Estela Noguera-Ortega, Maria Liousia, Miren L. Baroja, Jean M. Etersque, Jonathan Pham, Swarbhanu Sarkar, Beatriz M. Carreno, Gerald P. Linette, Ellen Puré, Steven M. Albelda, Mark A. Sellmyer
Journal: Molecular Therapy (2023)
Mesenchymal Stem Cell‐Derived Mitochondria Enhance Extracellular Matrix‐Derived Grafts for the Repair of Nerve Defect
Authors: Jun Bai, Bingbing Yu, Chaochao Li, Haofeng Cheng, Yanjun Guan, Zhiqi Ren, Tieyuan Zhang, Xiangyu Song, Zhibo Jia, Tianqi Su, Benzhang Tao, Haihao Gao, Boyao Yang, Lijing Liang, Xing Xiong, Xingyu Zhou, Lan Yin, Jiang Peng, Aijia Shang, Yu Wang
Journal: Advanced Healthcare Materials (2023)

Abstract Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High‐purity functional mitochondria with an intact structure are extracted from human umbilical cord‐derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC‐derived mitochondria (hUCMSC‐Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC‐Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC‐Mito‐loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair.
Complement alternative pathway determines disease susceptibility and severity in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis
Authors: Laura Lucientes-Continente, Gema Fernández-Juárez, Bárbara Márquez-Tirado, Laura Jiménez-Villegas, Mercedes Acevedo, Teresa Cavero, Luís Sánchez Cámara, Juliana Draibe, Paula Anton-Pampols, Fernando Caravaca-Fontán, Manuel Praga, Javier Villacorta, Elena Goicoechea de Jorge
Journal: Kidney International (2023)

Activation of the alternative pathway (AP) of complement is involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although the underlying molecular mechanisms are unclear. To gain insight into the role of the AP, common gene variants in CFH/CFHR1-5, CFB, C3 and MCP, and longitudinal determinations of plasma C3, C4, FH, FHR-1, FHR-2, FHR-5, FB, properdin and sC5b-9 levels were analyzed in a Spanish AAV cohort consisting of 102 patients; 54 with active AAV (active cohort) and 48 in remission not receiving immunosuppressants or dialysis therapy (remission cohort). The validation cohort consisted of 100 patients with ANCA-associated glomerulonephritis. Here, we demonstrated that common genetic variants in complement components of the AP are associated with disease susceptibility (CFB32Q/W) or severity of kidney damage in AAV (CFH-H1, CFH1H2 and ΔCFHR3/1). Plasma levels of complement components were significantly different between active and remission cohorts. In longitudinal observations, a high degree of AP activation at diagnosis was associated with worse disease outcome, while high basal FHR-1 levels and lower FH/FHR-1 ratios determined severe forms of kidney associated AAV. These genetic and plasmatic findings were confirmed in the validation cohort. Additionally, autoantibodies against FH and C3 convertase were identified in one and five active patients, respectively. Thus, our study identified key genetic and plasma components of the AP that determine disease susceptibility, prognosis, and severity in AAV. Our data also suggests that balance between FH and FHR-1 is critical and supports FHR-1 as a novel AP-specific therapeutic target in AAV.
IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab
Authors: Jiaqi Yu, Bing Yan, Shen Shen, Yang Wang, Ying Li, Feifei Cao, Wei Xiong, Yingshi Piao, Chen Hu, Ying Sun, Luo Zhang, Chengshuo Wang
Journal: Journal of Allergy and Clinical Immunology (2023)
Can liquid biopsies for MASH help increase the penetration of metabolic surgery? A narrative review
Authors: Lidia Castagneto-Gissey, Stefan R. Bornstein, Geltrude Mingrone
Journal: Metabolism (2023)

This narrative review highlights current evidence on non-invasive tests to predict the presence or absence as well as the severity of metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition characterized by fat accumulation in the liver that affects 32 % of the world population. The most severe form of MASLD is MASH in which hepatocyte ballooning and inflammation are present together with steatosis; MASH is often associated with liver fibrosis. MASH diagnosis is determined by invasive liver biopsy. Hence, there is a critical need for non-invasive MASH tests. Plasma biomarkers for MASH diagnosis generally have low sensitivity (62–66 %), and specificity (78–82 %). Monocyte levels of Perilipin2 (PLIN2) predict MASH with an accuracy of 92–93 %, and sensitivity and specificity of 90–95 % and 88–100 %, respectively. This liquid biopsy test can facilitate the study of MASH prevalence in general populations and also monitor the effects of lifestyle, surgical, and pharmacological interventions. Without any FDA-approved MASH therapeutic, and with metabolic surgery markedly surpassing the efficacy of lifestyle modification, an accurate and reliable liquid biopsy could help more people choose surgery as a treatment for MASH.
Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy
Authors: Rustum Karanjia, Alfredo A. Sadun
Journal: Ophthalmology (2023)

This study aimed to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber hereditary optic neuropathy (LHON).
Prostate-Specific Membrane Antigen–Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of <sup>225</sup>Ac-J591
Authors: Scott T. Tagawa, Charlene Thomas, A. Oliver Sartor, Michael Sun, Judith Stangl-Kremser, Mahelia Bissassar, Shankar Vallabhajosula, Sandra Huicochea Castellanos, Jones T. Nauseef, Cora N. Sternberg, Ana Molina, Karla Ballman, David M. Nanus, Joseph R. Osborne, Neil H. Bander
Journal: Journal of Clinical Oncology (2023)

PURPOSE Novel therapies are needed to extend survival in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA), a cell surface antigen overexpressed in PC, provides a validated target. This dose-escalation study investigated the safety, efficacy, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) for 225 Ac-J591, anti-PSMA monoclonal antibody J591 radiolabeled with the alpha emitter actinium-225. METHODS Following investigational new drug-enabling preclinical studies, we enrolled patients with progressive mCRPC that was refractory to or who refused standard treatment options (including androgen receptor pathway inhibitor and had received or been deemed ineligible for taxane chemotherapy). No selection for PSMA was performed. Patients received a single dose of 225 Ac-J591 at one of seven dose-escalation levels followed by expansion at the highest dose. Primary end point of dose-escalation cohort was determination of dose-limiting toxicity (DLT) and RP2D. RESULTS Radiochemistry and animal studies were favorable. Thirty-two patients received 225 Ac-J591 in an accelerated dose-escalation design (22 in dose escalation, 10 in expansion). One patient (1 of 22; 4.5%) experienced DLT in cohort 6 (80 KBq/kg) but none in cohort 7; MTD was not reached, and RP2D was the highest dose level (93.3 KBq/kg). The majority of high-grade adverse events (AEs) were hematologic with an apparent relationship with administered radioactivity. Nonhematologic AEs were generally of low grade. Prostate-specific antigen (PSA) declines and circulating tumor cell (CTC) control were observed: 46.9% had at least 50% PSA decline at any time (34.4% confirmed PSA response), and protocol-defined CTC count response occurred in 13 of 22 (59.1%). CONCLUSION To our knowledge, this is the first-in-human phase I dose-escalation trial of a single dose of 225 Ac-J591 in 32 patients with pretreated progressive mCRPC demonstrated safety and preliminary efficacy signals. Further investigation is underway.
Regulatory T cells shield muscle mitochondria from interferon-γ–mediated damage to promote the beneficial effects of exercise
Authors: P. Kent Langston, Yizhi Sun, Birgitta A. Ryback, Amber L. Mueller, Bruce M. Spiegelman, Christophe Benoist, Diane Mathis
Journal: Science Immunology (2023)

Exercise enhances physical performance and reduces the risk of many disorders such as cardiovascular disease, type 2 diabetes, dementia, and cancer. Exercise characteristically incites an inflammatory response, notably in skeletal muscles. Although some effector mechanisms have been identified, regulatory elements activated in response to exercise remain obscure. Here, we have addressed the roles of Foxp3 + CD4 + regulatory T cells (T regs ) in the healthful activities of exercise via immunologic, transcriptomic, histologic, metabolic, and biochemical analyses of acute and chronic exercise models in mice. Exercise rapidly induced expansion of the muscle T reg compartment, thereby guarding against overexuberant production of interferon-γ and consequent metabolic disruptions, particularly mitochondrial aberrancies. The performance-enhancing effects of exercise training were dampened in the absence of T regs . Thus, exercise is a natural T reg booster with therapeutic potential in disease and aging contexts.
CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration after radiation-induced injury
Authors: John G. McKendrick, Gareth-Rhys Jones, Sonia S. Elder, Erin Watson, Wouter T’Jonck, Ella Mercer, Marlene S. Magalhaes, Cecilia Rocchi, Lizi M. Hegarty, Amanda L. Johnson, Christoph Schneider, Burkhard Becher, Clare Pridans, Neil Mabbott, Zhaoyuan Liu, Florent Ginhoux, Marc Bajenoff, Rebecca Gentek, Calum C. Bain, Elaine Emmerson
Journal: Science Immunology (2023)

The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant immune cell in the salivary glands and are attractive therapeutic targets due to their unrivaled capacity to drive tissue repair. Yet, the nature and role of macrophages in salivary gland homeostasis and how they may contribute to tissue repair after injury are not well understood. Here, we show that at least two phenotypically and transcriptionally distinct CX3CR1